title: Potential therapeutic value of dendritic cells loaded with NY‑ESO‑1 protein for the immunotherapy of advanced hepatocellular carcinoma.
abstract: NY‑ESO‑1 is one of the most immunogenic cancer-testis (CT) antigens. Cancer vaccine trials based on NY‑ESO‑1 are currently ongoing. Dendritic cells (DCs) are the most potent antigen-presenting cells. The immune functions of DCs in a number of tumors have been identified; however, the potential therapeutic value of DCs pulsed with NY‑ESO‑1 in hepatocellular carcinoma (HCC) has not been extensively investigated. The objectives of the present study were to evaluate T cell response following stimulation with DCs pulsed with the recombinant NY‑ESO‑1 protein (rESO) and to establish a correlation between NY‑ESO‑1 expression and clinicopathological features in HCC patients. DCs were generated with granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL‑4) from human peripheral blood mononuclear cells. A mixed T cell reaction with DCs loaded with recombinant NY‑ESO‑1 protein (rESO-DCs) was evaluated by MTT assay. T cell responses against HCC cell lines were analyzed by measuring lactate dehydrogenase (LDH) activity. The protein levels of NY‑ESO‑1 were detected by immunohistochemistry (IHC) in a tissue microarray (TMA) containing 190 HCC samples. NY‑ESO‑1 transcript abundance was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 54 out of the 190 HCC samples. The results revealed that mature DCs were induced and that rESO‑DCs significantly stimulated T cell proliferation. The specific lysis of T cells stimulated with rESO‑DCs was significantly higher in the NY‑ESO‑1-positive HCC cells compared with the NY‑ESO‑1-negative cells and the other controls (p<0.01). NY‑ESO‑1 was expressed in 15.8% (30/190)of the HCC samples, as shown by IHC and in 24.1% (13/54) of the samples, as shown by RT-PCR. The frequency of NY‑ESO‑1 expression was significantly higher in HCC patients with portal vein tumor thrombosis (24.6%) compared with those without thrombosis (11.2%, p=0.013). Our data suggest that DCs loaded with NY‑ESO‑1 protein stimulate antigen-specific T cell responses against HCC cells in vitro. NY‑ESO‑1 may thus be used as a potential target for immunotherapy in advanced HCC.
authors.affiliation: Department of Pathology, Fujian Medical University, Fuzhou, Fujian 350004 P.R. China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Aimin
authors.initials: A
authors.lastname: Huang
authors.forename: Meiqin
authors.initials: M
authors.lastname: Gao
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Yan
authors.forename: Wenmin
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger